OBJECTIVE: We evaluated whether statins, in view of their
anti-inflammatory properties, may effectively prevent the onset or
modulate the severity of muscle wasting during cancer cachexia.
METHODS:
Simvastatin was administered to rats bearing the Yoshida AH-130 ascites
hepatoma, a well-studied cytokine-dependent experimental model of
cancer
cachexia. RESULTS: Quite surprisingly, the drug negatively affected the
wasting pattern induced by the AH-130 hepatoma. In fact, the
administration of simvastatin to tumor hosts induced a further weight
reduction of all the tissues examined except for the soleus, in the
absence of significant effects of simvastatin on tumor growth or on
food
intake. No effects were observed after simvastatin administration in
control animals, with the exception of a significant (P < 0.05)
reduction in heart weight. CONCLUSIONS: Simvastatin administration,
although capable of negatively modulating the inflammatory response,
did
not prevent muscle wasting in this experimental model of cancer
cachexia. Moreover, the further muscle loss observed in
simvastatin-treated tumor-bearing animals suggests that a note of
caution should be introduced in treating cancer patients with statins
in
view of the possible occurrence of harmful side effects.

PMID: 14624942 [PubMed - indexed for MEDLINE]

Again, an interesting study and, obviously, you are not Sharon (LOL).
I'll ask again for Sharon to supply the links to these statements she
made:

"A recently published medical journal article showed 100% of statin
patients have muscle damage identifiable on muscle biopsy after only a
few months.

Another recently published study showed all statin patients have
measurable cognitive impacts after 6 months.

Another recently published study showed neuropathy 26 times more likely
in statin patients."

I would think she's seen this by now, even though she's killfiled me.
We've heard from David, from Matti and now from Bill. I'm honestly
interested in seeing the actual article and studies from which she based
her statements.

"Muscle pain and weakness are frequent complaints in patients
receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase
inhibitors (statins). Many patients with myalgia have creatine
kinase levels that are either normal or only marginally
elevated, and no obvious structural defects have been reported
in patients with myalgia only. To investigate further the
mechanism that mediates statin-induced skeletal muscle damage,
skeletal muscle biopsies from statin-treated and non-statin-
treated patients were examined using both electron microscopy
and biochemical approaches. The present paper reports clear
evidence of skeletal muscle damage in statin-treated patients,
despite their being asymptomatic. Though the degree of overall
damage is slight, it has a characteristic pattern that includes
breakdown of the T-tubular system and subsarcolemmal rupture.
These characteristic structural abnormalities observed in the
statin-treated patients were reproduced by extraction of
cholesterol from skeletal muscle fibres in vitro. These
findings support the hypothesis that statin-induced cholesterol
lowering per se contributes to myocyte damage and suggest
further that it is the specific lipid/protein organization of
the skeletal muscle cell itself that renders it particularly
vulnerable.

[...]

... We collected skeletal muscle samples from a total of 22
individuals, including 14 who were receiving treatment with HMG
CoA reductase inhibitors for hypercholesterolaemia and eight
individuals who had not received statin treatment and served as
controls. None of the patients had a previous history of
rhabdomyalgia or weakness. ...

[...]

Skeletal muscle biopsies from a total of 14 patients treated with
pravastatin (n = 2), atorvastatin (n = 4), or simvastatin (n =
and eight individuals without statin treatment underwent
morphological evaluation, analysis of membrane-lipid contents as
well as quantification of levels of mRNA abundance of six
cholesterol-associated proteins (Table 1). None of our patients
was treated with fibrates, which are known to potentiate myopathy
in statin-treated patients, and one individual was prescribed
ezetimibe (Table 1). Other relevant concomitant medications
include Ca2+-channel blockers (n = 4), cyclosporin (n = 1),
cephalosporin (n = , digoxin (n = 1), and warfarin (n = 7), all
of which are known to interfere with statin metabolism [20].

Morphological analysis demonstrated that the structural integrity
of skeletal muscle fibres was compromised in 10 of 14 of the
statin-treated patients and in only one of eight controls (Table
1; p = 0.02)."

There were no apparent differences in the degree of muscle injury
observed in the statin-treated patients taking each specific
statin, but these patient groups were quite small."

So the muscle damage seems to be very common even in cases, where
there are no symptoms. Still, it does dot seem to occur in all statin
users, but perhaps in majority of them: in this smalla study in 71% of
statin users.

Another recently published study showed all statin patients have measurable
cognitive impacts after 6 months.

The articles about the cognitive effects of statins are conflicting.
Both cognitive impairment and benefits have been reported. In any case
effects seem to be small. It may be possible that for different
populations and individuals the effects may be opposite. The effects
may also depend of the statin used. Here some of the articles:

"... Overall, none of these studies reported finding a positive
benefit for any statin on cognition in non-demented subjects
although there was inconsistent evidence for acute cognitive
worsening in some studies. ..."

"CONCLUSION: This study provides partial support for minor
decrements in cognitive functioning with statins. Whether such
effects have any long-term sequelae or occur with other
cholesterol-lowering interventions is not known."

"CONCLUSION: Current literature is conflicting with regard to
the effects of statins on memory loss. Experimental studies
support links between cholesterol intake and amyloid synthesis;
observational studies indicate that patients receiving statins
have a reduced risk of dementia. However, available prospective
studies show no cognitive or antiamyloid benefits for any
statin. In addition, case reports raise the possibility that
statins, in rare cases, may be associated with cognitive
impairment, though causality is not certain."

"The statins are widely used to treat dyslipidemias. They are
generally associated with mild adverse effects, but rarely, more
serious reactions may occur. A 51-year-old man experienced
delayed-onset, progressive memory loss while receiving simvastatin
for hypercholesterolemia. His therapy was switched to pravastatin,
and memory loss resolved gradually over the next month, with no
recurrence of the adverse effect."

"Conclusion: Statin drug use was associated with a slight
reduction in cognitive decline in an elderly population. This
relationship could not be completely explained by the effect of
statins on lowering of serum cholesterol."

"CONCLUSION: The present study concludes that there are
significant beneficial effects of atorvastatin in a dose of 10
mg/day for a period of 6 months on higher functions as measured by
the above standard neurocognitive tests."

"CONCLUSION: Lipid-lowering drugs--in particular, the
statins--seem to lower the odds of developing cognitive
impairment. Randomized, controlled trials are needed to address
the efficacy of these agents specifically in different types of
dementia."

Another recently published study showed neuropathy 26 times more likely in
statin patients."

Neuropathy is a very rare side effect, but when it happens, it could
be crippling. I know about a person, who after starting statin therapy
lost the use of his legs so that he can no longer walk. Still,
according the following study statin use increases the risk of
neurpathy only by a factor of 1.3 and not 26-fold:

OBJECTIVE: We evaluated whether statins, in view of their
anti-inflammatory properties, may effectively prevent the onset or
modulate the severity of muscle wasting during cancer cachexia. METHODS:
Simvastatin was administered to rats bearing the Yoshida AH-130 ascites
hepatoma, a well-studied cytokine-dependent experimental model of cancer
cachexia. RESULTS: Quite surprisingly, the drug negatively affected the
wasting pattern induced by the AH-130 hepatoma. In fact, the
administration of simvastatin to tumor hosts induced a further weight
reduction of all the tissues examined except for the soleus, in the
absence of significant effects of simvastatin on tumor growth or on food
intake. No effects were observed after simvastatin administration in
control animals, with the exception of a significant (P < 0.05)
reduction in heart weight. CONCLUSIONS: Simvastatin administration,
although capable of negatively modulating the inflammatory response, did
not prevent muscle wasting in this experimental model of cancer
cachexia. Moreover, the further muscle loss observed in
simvastatin-treated tumor-bearing animals suggests that a note of
caution should be introduced in treating cancer patients with statins in
view of the possible occurrence of harmful side effects.

PMID: 14624942 [PubMed - indexed for MEDLINE]

--
S Jersey USA Zone 5 Shade
This article is posted under fair use rules in accordance with
Title 17 U.S.C. Section 107, and is strictly for the educational
and informative purposes. This material is distributed without profit.

"Muscle pain and weakness are frequent complaints in patients
receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase
inhibitors (statins). Many patients with myalgia have creatine
kinase levels that are either normal or only marginally
elevated, and no obvious structural defects have been reported
in patients with myalgia only. To investigate further the
mechanism that mediates statin-induced skeletal muscle damage,
skeletal muscle biopsies from statin-treated and non-statin-
treated patients were examined using both electron microscopy
and biochemical approaches. The present paper reports clear
evidence of skeletal muscle damage in statin-treated patients,
despite their being asymptomatic. Though the degree of overall
damage is slight, it has a characteristic pattern that includes
breakdown of the T-tubular system and subsarcolemmal rupture.
These characteristic structural abnormalities observed in the
statin-treated patients were reproduced by extraction of
cholesterol from skeletal muscle fibres in vitro. These
findings support the hypothesis that statin-induced cholesterol
lowering per se contributes to myocyte damage and suggest
further that it is the specific lipid/protein organization of
the skeletal muscle cell itself that renders it particularly
vulnerable.

[...]

... We collected skeletal muscle samples from a total of 22
individuals, including 14 who were receiving treatment with HMG
CoA reductase inhibitors for hypercholesterolaemia and eight
individuals who had not received statin treatment and served as
controls. None of the patients had a previous history of
rhabdomyalgia or weakness. ...

[...]

Skeletal muscle biopsies from a total of 14 patients treated with
pravastatin (n = 2), atorvastatin (n = 4), or simvastatin (n =
and eight individuals without statin treatment underwent
morphological evaluation, analysis of membrane-lipid contents as
well as quantification of levels of mRNA abundance of six
cholesterol-associated proteins (Table 1). None of our patients
was treated with fibrates, which are known to potentiate myopathy
in statin-treated patients, and one individual was prescribed
ezetimibe (Table 1). Other relevant concomitant medications
include Ca2+-channel blockers (n = 4), cyclosporin (n = 1),
cephalosporin (n = , digoxin (n = 1), and warfarin (n = 7), all
of which are known to interfere with statin metabolism [20].

Morphological analysis demonstrated that the structural integrity
of skeletal muscle fibres was compromised in 10 of 14 of the
statin-treated patients and in only one of eight controls (Table
1; p = 0.02)."

There were no apparent differences in the degree of muscle injury
observed in the statin-treated patients taking each specific
statin, but these patient groups were quite small."

So the muscle damage seems to be very common even in cases, where
there are no symptoms. Still, it does dot seem to occur in all statin
users, but perhaps in majority of them: in this smalla study in 71% of
statin users.

Quote:

Another recently published study showed all statin patients have measurable
cognitive impacts after 6 months.

The articles about the cognitive effects of statins are conflicting.

Both cognitive impairment and benefits have been reported. In any case
effects seem to be small. It may be possible that for different
populations and individuals the effects may be opposite. The effects
may also depend of the statin used. Here some of the articles:

"... Overall, none of these studies reported finding a positive
benefit for any statin on cognition in non-demented subjects
although there was inconsistent evidence for acute cognitive
worsening in some studies. ..."

"CONCLUSION: This study provides partial support for minor
decrements in cognitive functioning with statins. Whether such
effects have any long-term sequelae or occur with other
cholesterol-lowering interventions is not known."

"CONCLUSION: Current literature is conflicting with regard to
the effects of statins on memory loss. Experimental studies
support links between cholesterol intake and amyloid synthesis;
observational studies indicate that patients receiving statins
have a reduced risk of dementia. However, available prospective
studies show no cognitive or antiamyloid benefits for any
statin. In addition, case reports raise the possibility that
statins, in rare cases, may be associated with cognitive
impairment, though causality is not certain."

"The statins are widely used to treat dyslipidemias. They are
generally associated with mild adverse effects, but rarely, more
serious reactions may occur. A 51-year-old man experienced
delayed-onset, progressive memory loss while receiving simvastatin
for hypercholesterolemia. His therapy was switched to pravastatin,
and memory loss resolved gradually over the next month, with no
recurrence of the adverse effect."

"Conclusion: Statin drug use was associated with a slight
reduction in cognitive decline in an elderly population. This
relationship could not be completely explained by the effect of
statins on lowering of serum cholesterol."

"CONCLUSION: The present study concludes that there are
significant beneficial effects of atorvastatin in a dose of 10
mg/day for a period of 6 months on higher functions as measured by
the above standard neurocognitive tests."

"CONCLUSION: Lipid-lowering drugs--in particular, the
statins--seem to lower the odds of developing cognitive
impairment. Randomized, controlled trials are needed to address
the efficacy of these agents specifically in different types of
dementia."

Quote:

Another recently published study showed neuropathy 26 times more likely in
statin patients."

Neuropathy is a very rare side effect, but when it happens, it could

be crippling. I know about a person, who after starting statin therapy
lost the use of his legs so that he can no longer walk. Still,
according the following study statin use increases the risk of
neurpathy only by a factor of 1.3 and not 26-fold: